The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release - II. Interaction of Alkali and Alkaline Earth Cations

Glucose-induced insulin secretion is enhanced at high K + concentrations (10 to 34 mEq/l), and in the presence of ouabain. It is reduced when Na + is partially replaced by either Li + , Tris, or larger amounts of K + (87 to 115 mEq/l). The elevated rate of secretion observed at high K + concentration (24 mEq/l) is markedly reduced by replacement of NaCl by sucrose. These data suggest that Na + entry in the beta-cell favors insulin release. However, the stimulant action of glucose is increased when Na + is replaced by choline and persists in a Na + -free medium, indicating that the influx of Na + per se is not necessary for secretion to occur. It is suggested that alkali cations could influence insulin secretion through an altered handling of alkaline earth cations by the beta-cell. In favor of this hypothesis, it is shown that the beta-cell becomes unresponsive to Ba++ when Na+ is replaced by Li+, Tris, or large amounts of K+; whereas the elevated rates of secretion observed when Na + is replaced by choline or moderate amounts of K + are markedly reduced by the omission of Ca ++ from the incubation medium. The inhibitory effect of extracellular acidosis upon glucose-induced secretion could also be due, in part at least, to a reduced entry of Ca ++ in the beta-cell. These data support the concept that entry of Ca ++ might trigger the release of insulin and that the influence of alkali cations upon insulin release could be mediated by an alteration of this process.